Inside the Thrombus: Association of Hemostatic Parameters With Outcomes in Large Vessel Stroke Patients

Abstract

Background: Actual clinical management of ischemic stroke (IS) is based on restoring cerebral blood flow using tissue plasminogen activator (tPA) and/or endovascular treatment (EVT). Mechanical thrombectomy has permitted the analysis of thrombus structural and cellular classic components. Nevertheless, histological assessment of hemostatic parameters such as thrombin-activatable fibrinolysis inhibitor (TAFI) and matrix metalloproteinase 10 (MMP-10) remains unknown, although their presence could determine thrombus stability and its response to thrombolytic treatment, improving patient's outcome.Methods: We collected thrombi (n = 45) from large vessel occlusion (LVO) stroke patients (n = 53) and performed a histological analysis of different hemostatic parameters [TAFI, MMP-10, von Willebrand factor (VWF), and fibrin] and cellular components (erythrocytes, leukocytes, macrophages, lymphocytes, and platelets). Additionally, we evaluated the association of these parameters with plasma levels of MMP-10, TAFI and VWF activity and recorded clinical variables.Results: In this study, we report for the first time the presence of MMP-10 and TAFI in all thrombi collected from LVO patients. Both proteins were localized in regions of inflammatory cells, surrounded by erythrocyte and platelet-rich areas, and their content was significantly associated (r = 0.41, p < 0.01). Thrombus TAFI was lower in patients who died during the first 3 months after stroke onset [odds ratio (OR) (95%CI); 0.59 (0.36–0.98), p = 0.043]. Likewise, we observed that thrombus MMP-10 was inversely correlated with the amount of VWF (r = −0.30, p < 0.05). Besides, VWF was associated with the presence of leukocytes (r = 0.37, p < 0.05), platelets (r = 0.32, p < 0.05), and 3 months mortality [OR (95%CI); 4.5 (1.2–17.1), p = 0.029]. Finally, plasma levels of TAFI correlated with circulating and thrombus platelets, while plasma MMP-10 was associated with cardiovascular risk factors and functional dependence at 3 months.Conclusions: The present study suggests that the composition and distribution of thrombus hemostatic components might have clinical impact by influencing the response to pharmacological and mechanical therapies as well as guiding the development of new therapeutic strategies.

Platelet-to-lymphocyte ratio at 24h after thrombolysis is a prognostic marker in acute ischemic stroke patients

“…Moreover, the mechanisms by which the prognostic value of the 24-h PLR after rtPA appears to be greater than that at baseline have not been well established. An increase in platelet count after thrombolytic therapy may be responsible for delayed thrombosis, leading to reocclusion and rethrombosis ( 31 ). A previous study revealed that rtPA potentially induces the elevation of matrix metalloproteinase-9 and chemokine ligand-2, which mediate blood–brain barrier disruption and may lead to hemorrhagic transformation.…”

Identification of Genes and miRNAs Associated with TAFI-Related Thrombosis: An in Silico Study

“…Matrix metalloproteinase-10 (MMP-10) and TAFI have been shown to colocalize with inflammatory cells and platelets in all thrombi retrieved from large vessel occlusion stroke patients [ 50 ]. Most importantly, subjects who died within 3 months had higher VWF and lower TAFI content in thrombi, suggesting that the histological composition and distribution of different thrombi hemostatic components have prognostic and therapeutic implications [ 50 ]. Two recent reviews have highlighted the impact of thrombus composition and organization on the efficacy of thrombolysis in the setting of acute ischemic stroke (AIS) [ 51 , 52 ].…”